To study the dynamic properties and failure characteristics of karst cave roof under combined action of pile load and earthquake, supported by the pile foundation project of the Zhoujiawan Bridge of the Chongqing-Guizhou Railway, the main control parameters of rock materials, model piles, and seismic waves were determined based on the separation similarity method. Through 19 groups of mixture ratio tests, the index of the similar material ratios of rock masses used in shaking table tests were obtained, and the small-scale shaking table model tests of karst pile foundation were conducted considering the influence of different thicknesses of the roof and diameters of the cave. The results showed that the existence of caves changed the local fundamental frequency and dynamic characteristics of the model, and it hindered the transmission of seismic waves and dissipated energy. The frequency spectrum of the wave had no direct relation with the size of the upper load. The cracks in the pile-end caused by the combined action of the pile-end load and the earthquake gave rise to the overall amplitude decrease of the seismic waves, which caused the change of the fundamental frequency of the model. The internal cracks in the model increased with the enhancement of the acceleration of the seismic waves, resulting in a progressive increase in the damping ratio, which caused the main frequency of the vibration to decrease. Variation of the same kind of seismic wave only altered the wave amplitude, while different kinds of seismic waves led to the distribution changes of the fundamental frequency. The strain of the monitoring point increased with the increment of the peak of the seismic waves. Shearing failure of the karst roof occurred when the diameter of the cave was small, but punching-shearing failure happened when the diameter was larger.